title: Mammaglobin B (SCGB2A1) is a novel tumour antigen highly differentially expressed in all major histological types of ovarian cancer: implications for ovarian cancer immunotherapy.
abstract: BACKGROUND
  We studied the genetic fingerprints of ovarian cancer and validated the potential of Mammaglobin b (SCGB2A1), one of the top differentially expressed genes found in our analysis, as a novel ovarian tumour rejection antigen.
  
  
  METHODS
  We profiled 70 ovarian carcinomas including 24 serous (OSPC), 15 clear-cell (CC), 24 endometrioid (EAC) and 7 poorly differentiated tumours, and 14 normal human ovarian surface epithelial (HOSE) control cell lines using the Human HG-U133 Plus 2.0 chip (Affymetrix). Quantitative real-time PCR and immunohistochemistry staining techniques were used to validate microarray data at RNA and protein levels for SCGB2A1. Full-length human-recombinant SCGB2A1 was used to pulse monocyte-derived dendritic cells (DCs) to stimulate autologous SCGB2A1-specific cytotoxic T-lymphocyte (CTL) responses against chemo-naive and chemo-resistant autologous ovarian tumours.
  
  
  RESULTS
  Gene expression profiling identified SCGB2A1 as a top differentially expressed gene in all histological ovarian cancer types tested. The CD8+ CTL populations generated against SCGB2A1 were able to consistently induce lysis of autologous primary (chemo-naive) and metastatic/recurrent (chemo-resistant) target tumour cells expressing SCGB2A1, whereas autologous HLA-identical noncancerous cells were not lysed. Cytotoxicity against autologous tumour cells was significantly inhibited by anti-HLA-class I (W6/32) monoclonal antibody. Intracellular cytokine expression measured by flow cytometry showed a striking type 1 cytokine profile (i.e., high IFN-γ secretion) in SCGB2A1-specific CTLs.
  
  
  CONCLUSIONS
  SCGB2A1 is a top differentially expressed gene in all major histological types of ovarian cancers and may represent a novel and attractive target for the immunotherapy of patients harbouring recurrent disease resistant to chemotherapy.
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520-8063, USA.
authors.forename: S
authors.initials: S
authors.lastname: Bellone
authors.forename: R
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authors.lastname: Tassi
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authors.lastname: Betti
authors.forename: D
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authors.lastname: English
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authors.lastname: Cocco
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authors.lastname: Gasparrini
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authors.lastname: Bortolomai
authors.forename: J D
authors.initials: JD
authors.lastname: Black
authors.forename: P
authors.initials: P
authors.lastname: Todeschini
authors.forename: C
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authors.lastname: Romani
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authors.lastname: Ravaggi
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authors.lastname: Bignotti
authors.forename: E
authors.initials: E
authors.lastname: Bandiera
authors.forename: L
authors.initials: L
authors.lastname: Zanotti
authors.forename: S
authors.initials: S
authors.lastname: Pecorelli
authors.forename: L
authors.initials: L
authors.lastname: Ardighieri
authors.forename: M
authors.initials: M
authors.lastname: Falchetti
authors.forename: C
authors.initials: C
authors.lastname: Donzelli
authors.forename: E R
authors.initials: ER
authors.lastname: Siegel
authors.forename: M
authors.initials: M
authors.lastname: Azodi
authors.forename: D-A
authors.initials: DA
authors.lastname: Silasi
authors.forename: E
authors.initials: E
authors.lastname: Ratner
authors.forename: P E
authors.initials: PE
authors.lastname: Schwartz
authors.forename: T J
authors.initials: TJ
authors.lastname: Rutherford
authors.forename: A D
authors.initials: AD
authors.lastname: Santin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007167:Immunotherapy; D060788:Mammaglobin B / Q000235:genetics / Q000378:metabolism*; D046228:Microarray Analysis; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D059467:Transcriptome; D054928:Validation Studies as Topic
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D060788:Mammaglobin B; C556467:SCGB2A1 protein, human